Explore recent mRNA, saRNA, circular RNA, and LNP research on delivery, therapeutic translation, safety, analytical characterization, and manufacturing.
Selected for substantive contributions to delivery, translation, analytics, manufacturing, and safety. Original publication dates and evidence levels are retained. This library covers the latest 120 days; individual published guides remain available.
McMillan C; Hussain M; Punnabhum P; Varley AJ; Kong KYS; Rattray Z; Druschitz A; Perrie Y Journal of controlled release : official journal of the Controlled Release Society · DOI 10.1016/j.jconrel.2026.115418
Using a common ALC-0315 formulation, the study compared reporter expression from conventional mRNA, self-amplifying RNA, and plasmid DNA, individually and in combinations. Mouse experiments showed distinct timing and duration associated with payload identity. Mixed preparations generally behaved additively under the tested conditions. The work helps separate cargo effects from formulation effects, without establishing universal expression profiles across doses, tissues, or products.
Why it is included: Improves interpretation of payload-dependent expression kinetics; one formulation and reporter system cannot define performance across all therapeutic cargoes or routes.
Abdulraouf M. Abbas; Ramy Ghanim; Sebastian Rudden; David Schultz; Bora Jang; Avraham Shakked; Hyejin Kim; James E. Dahlman; Alex Abramson ACS nano · DOI 10.1021/acsnano.5c18549
Investigators administered nanoparticles to several gastrointestinal submucosal sites to examine route-dependent targeting. Gastric delivery increased pancreatic exposure in rodents, while GLP-1 mRNA improved glucose regulation in mice. Buccal administration supported local and lymphatic targeting with vaccine responses. These are tissue-directed administration experiments; they do not establish that conventional swallowed nanoparticles can survive digestion and reproduce the same delivery profile.
Why it is included: Shows how gastrointestinal administration can redirect distribution; submucosal delivery in rodents is distinct from a validated oral capsule or human metabolic therapy.
Songtao Dong; Fanglin Gong; Tyler Thomson; Yunshu Cai; Lauren Healy; Rick X. Z. Lu; Ziyu Zhou; Yue Xu; Jingan Chen; Margarita Savguira; Xianglei Fu; Sijin Luozhong; Muye Zhou; Payton Kirtley; Brandon K. Wilder; Bowen Li Nature biotechnology · DOI 10.1038/s41587-026-03298-8
A lipid screen explicitly incorporated a large base-editor transcript rather than relying on small reporter RNA. The lead lipid retained favorable RNA interactions and membrane-disrupting structure as cargo size increased. It improved editing in liver, brain, and lung using different administration routes, including intrathecal and intratracheal dosing. The findings do not establish systemic delivery to all three organs.
Why it is included: Makes cargo size a practical screening parameter for gene-editing formulations; tissue results depend on administration route and remain preclinical.
Yao Zhang; Jerry Leung; Judy Cheng; Arash Momeni; Albert Kamanzi; Ariadne Tuckmantel Bido; Suiyang Liao; Emma Kang; Colton Strong; Christian J. Kastrup; Sabrina Leslie; Miffy Hok Yan Cheng; Pieter R. Cullis Advanced Materials · DOI 10.1002/adma.75174
Researchers modified buffer exchange into a two-step dialysis process, first promoting fusion under acidic, higher-ionic-strength conditions while retaining ethanol, then removing ethanol and raising pH. Compared with one-step exchange, the process increased mRNA copies per particle, reduced empty particles, and improved transfection in cells and animals. These formulation-specific results do not establish that removing empties always improves every product.
Why it is included: Links particle-level loading with process conditions and function; scale-up requires controlling residual solvent, loading distributions, and consistent performance across batches.
Ha M; Kim J; Kim S; Naidu GS; Cho S; Yong SB Advanced science (Weinheim, Baden-Wurttemberg, Germany) · DOI 10.1002/advs.77923
Researchers incorporated an amphiphilic PD-L1 inhibitor as an additional nanoparticle component rather than administering it separately. The modified formulation increased lymph-node reporter expression and strengthened vaccine-associated immune responses in experimental models. Similar targeting effects were observed with two ionizable lipid backbones. These results suggest formulation-dependent immune targeting, without proving broad applicability or clinical benefit across tumor types.
Why it is included: Combines delivery engineering with checkpoint modulation; evidence from two lipid backbones does not establish universal targeting or clinical superiority.
Zixuan Zhen; Mittal Darji; Kuo-Chih Shih; Xinhao Lin; Rama Prajapati; Sheyda Ranjbar; Nirnoy Dan; Grace Shenouda; Jonathan Hu; Robin Bogner; Xiuling Lu Journal of Controlled Release · DOI 10.1016/j.jconrel.2026.115412
Researchers compared 12 lyophilized mRNA-LNP formulations containing sucrose, trehalose, and polyvinylpyrrolidone. A ternary protectant system at a 1:20 lipid-to-protectant ratio preserved particle properties, RNA integrity, and in vitro transfection after one month at 40°C. Sucrose crystallization reduced protection. The results show why physical measurements need functional confirmation and do not establish a clinical product shelf life.
Why it is included: Links protectant physical state with functional stability; formulation developers should combine particle and RNA measurements with potency under relevant storage conditions.
Yuxin He; Lin Wang; Abigael P. Williams; Trisha I. Valerio; Yuanhong Sun; James Bowman; Samantha D. Ricketts; Savannah Hammond; Aidan Sison; Jezan Alexandre; Zachary Niastor; Wei R. Chen; Dixy E. Green; Kar-Ming Fung; Paul L. DeAngelis; Stefan Wilhelm ACS nano · DOI 10.1021/acsnano.6c11865
Heparosan surface modification was compared with conventional PEG-based nanoparticles across several ionizable lipid formulations. Modified particles improved expression in immune-cell models and showed reduced association with late endosomes and lysosomes. Mouse experiments assessed repeated expression and vaccine antibody responses. The findings support an alternative surface-engineering approach, while long-term immunogenicity, biodistribution, and manufacturing consistency require additional study.
Why it is included: Expands surface-engineering options for immune delivery; trafficking correlations and short-term mouse tolerability do not establish long-term human safety or universal PEG replacement.
Researchers reorganized preformed nanoparticles so a metabolic RNA becomes available before the therapeutic payload. This staged architecture increased cellular energy availability and subsequent protein production. Mouse cancer and infectious-disease vaccine experiments showed improved immune activity, supporting spatial organization as an additional delivery design variable. Compatibility across several nucleic acid formats was demonstrated, but human performance remains untested.
Why it is included: Adds spatial RNA arrangement to formulation design; vaccine gains were demonstrated in mice and require independent replication and clinical validation.
Nageen Sardar; Shoaib Manzoor Human immunology · DOI 10.1016/j.humimm.2026.112083
This review compares self-amplifying and circular RNA vaccine architectures, expression kinetics, delivery approaches, and immune responses. It discusses the different reasons these platforms may extend antigen production or reduce dose requirements, alongside manufacturing, purity, reactogenicity, and regulatory challenges. It is a synthesis of heterogeneous preclinical and early clinical evidence, not a new head-to-head trial establishing superiority over conventional mRNA vaccines.
Why it is included: Useful for comparing next-generation RNA platforms; heterogeneous studies and limited clinical data prevent broad claims of superior durability or safety.
Rui Chen; Letao Xu; Alexander H. Staudacher; Xing Wang; Ruoxuan Jia; John W. Finnie; Xiaoyan Wang; Dawn M. Whelan; Michael P. Brown; Chun-Xia Zhao Science advances · DOI 10.1126/sciadv.aed9568
Antibody-coated nanoparticles targeted TREM2-expressing tumor-associated macrophages and combined CXCL9-encoding mRNA with a Toll-like receptor agonist. The approach remodeled the tumor immune environment and increased cytotoxic T-cell infiltration and activity. Additional checkpoint blockade strengthened immune responses in experimental models. This is a targeted delivery and combination-immunotherapy proof of concept, rather than evidence of efficacy in patients.
Why it is included: Connects macrophage targeting with local chemokine production; animal combination-treatment findings do not establish clinical benefit or the contribution of each component.
Kinnari Santosh Arte; Rachana Sapkota; Chanakya D. Patil; Yijing Huang; Eric J. Munson; Sajal Patel; Nicole Payton; Rushit Lodaya; Qi Tony Zhou; Li Lily Qu AAPS PharmSciTech · DOI 10.1208/s12249-026-03516-1
Using yeast RNA as a model payload, researchers evaluated atomization, freezing, drying temperature, and annealing during spray-freeze drying of RNA-LNPs. Powder diffraction, microscopy, and solid-state NMR supported characterization. Sucrose outperformed trehalose in the tested systems, and annealing improved stability. Because the payload was model RNA, these findings do not directly establish therapeutic mRNA expression potency or clinical-product stability.
Why it is included: Offers process guidance for solid RNA formulations; therapeutic mRNA translation requires additional integrity, functional potency, and product-specific stability studies.
Seong Gi Lim; Minju Lee; Yiming Wang; Eunjin Choi; Ji Sun Park; Kyungmin Park; Hayoung Jeon; Donghyun Kim; Donghyun Lee; Yeeun Lee; Kee‐Pyo Kim; Eunha Kim; Heebeom Koo Advanced science (Weinheim, Baden-Wurttemberg, Germany) · DOI 10.1002/advs.77387
The study introduces an ionizable lipid with two apparent ionization transitions that persist after nanoparticle formulation. Following intravenous administration, the particles favored pulmonary mRNA expression and improved outcomes in an experimental acute lung inflammation model. Simulations linked protonation states to membrane interactions. The work provides a mechanistic design hypothesis, with selectivity and tolerability established only in the tested preclinical settings.
Why it is included: Links ionization behavior to lung expression and intracellular release; mechanistic simulations and mouse efficacy require broader validation before translation.
